We are currently investigating the mechanisms by which diethylstilbestrol lowers the high serum enzymes present in children with Duchenne's muscular dystrophy. We have found no experimental evidence of enzyme inhibition, enhanced enzyme clearance, increased plasma volume, reduced muscle enzyme content to account for this reduction. On the other hand, we have found a 20 to 50 percent reduction in enzyme efflux from mouse muscle tested in vitro for 4 hours, after diethylstilbestrol treatment (10 micrograms/day/mouse) for 2 and 3 weeks, respectively. We are attempting to assess by what mechanism the in vitro efflux is reduced. This is being studied morphologically, using histological and ultrastructural methods; and chemically analyzing the lipid and phospholipid content of the sarcolemma; and with radioautographic studies to identify the site of diethylstilbestrol localization in skeletal muscle. In addition, we are investigating the basis of a variety of unusual characteristics noted in dystrophic human skeletal muscle grown in tissue culture. Our plan is to isolate normal and dystrophic human myoblasts under identical conditions to ascertain the reliability of these observations; and if possible to develop clones to study in a controlled fashion, the factors that influence myotube formation, growth, and differentiation; the chemical and enzymatic composition of normal and dystrophic human skeletal muscle without the presence of other contaminating cells; and finally assess the influence of potentially therapeutic agents on differences which may be noted.